Our research program will take several directions. First, we plan to further delineate the physiologic role of glucagon to better understand how the glucagon-secreting A-cell functions in harmony with the insulin-secreting B-cell as a bihormonal regulator of diabetic hyperglucagonemia to the metabolic derangements of diabetes and establish the efficacy of the pharmacologic suppression of glucagon secretion in the management of diabetes mellitus. An attempt will be made to ascertain whether the abnormal glucagon levels in human diabetes mellitus are the consequence only of insulin lack or whether, in addition to the well characterized consequences of insulin deficiency upon A-cell function, there is a defect in A-cell function in the diabetic patient which is independent and not correctable by insulin. Other planned areas of study include an examination of extrapancreatic A-cells and their function, a chracterization of the various IRG fractions in human plasma with regard to their biologic, immunologic and physiologic properties and their role in diabetes. Finally, we will investigate the somatostatin-containing D-cell and its relationship to normal A-cell and B-cell function and its role in abnormal A-cell and B-cell secretion.